Current Drug Research Reviews - Volume 14, Issue 2, 2022

Von Hippel-Lindau disease is an autosomal dominant disorder characterised by renal cell carcinomas, pancreatic neuroendocrine tumours, central nervous system hemangioblastomas, retinoblastomas, and tumours of the reproductive tract. This disease results from loss of function mutations in the tumour suppressor gene known as the Von Hippel-Lindau gene, located on chromosome 3. Loss of function mutation in the Von Hippel-Lindau gene results in the accumulation of a protein known as a hypoxia-inducible factor, which promotes cellular proliferation and angiogenesis, leading to cancer. Belzutifan inhibits the hypoxia-inducible factor by binding to the Per-ARNT -Sim-B binding pocket on the hypoxia-inducible factor -2α, inhibiting cellular proliferation and angiogenesis. In our thorough literature review, we identified 37 relevant articles. Belzutifan showed clinically meaningful response rates for both Von Hippel-Lindau disease-associated renal cell carcinomas and non-renal cell cancers. The pharmacokinetic profile of belzutifan was much better than its congener molecules due to the optimisation of its dihalide groups from germinal to vicinal. The pharmacodynamic effect of belzutifan was confirmed by its ability to decrease serum erythropoietin, which is a direct result of hypoxia-inducible factor- 2α inhibition. The significant side effects observed were anaemia, hypoxia, fatigue, hypertension, visual impairment and weight gain. Multiple clinical trials are currently underway to determine the role of beluztifan as part of combination regimens in treating Von Hippel-Lindau diseaseassociated malignancies.

Monoacylglycerol is a metabolic key serine hydrolase engaged in the regulation of the signalling network system of endocannabinoids, which is associated with various physiological processes like pain, inflammation, feeding cognition, and neurodegenerative diseases like Alzheimer’s and Parkinson’s disease. The monoacylglycerol was also found to act as a regulator and the free fatty acid provider in the proliferation of cancer cells as well as numerous aggressive tumours such as colorectal cancer, neuroblastoma, and nasopharyngeal carcinoma. It also played an important role in increasing the concentration of specific lipids derived from free fatty acids like phosphatidic acid, lysophosphatidic acid, sphingosine-1-phosphate, and prostaglandin E2. These signalling lipids are associated with cell proliferation, survival, tumour cell migration, contribution to tumour development, maturation, and metastases. In this study, we present a review on structurally diverse MAGL inhibitors, their development, and their evaluation for different pharmacological activities.

New drug development for a disease is a tedious, time-consuming, complex, and expensive process. Even if it is done, the chances for success of newly developed drugs are still very low. Modern reports state that repurposing the pre-existing drugs will have more efficient functioning than newly developed drugs. This repurposing process will save time, reduce expenses and provide more success rate. The only limitation for this repurposing is getting a desired pharmacological and characteristic parameter of various drugs from vast data about medications, their effects, and target mechanisms. This drawback can be avoided by introducing computational methods of analysis. This includes various network analysis types that use various biological processes and relationships with various drugs to simplify data interpretation. Some of the data sets now available in standard, and simplified forms include gene expression, drug-target interactions, protein networks, electronic health records, clinical trial results, and drug adverse event reports. Integrating various data sets and interpretation methods allows a more efficient and easy way to repurpose an exact drug for the desired target and effect. In this review, we are going to discuss briefly various computational biological network analysis methods like gene regulatory networks, metabolic networks, protein-protein interaction networks, drug-target interaction networks, drugdisease association networks, drug-drug interaction networks, drug-side effects networks, integrated network-based methods, semantic link networks, and isoform-isoform networks. Along with this, we briefly discussed the drug's limitations, prediction methodologies, and data sets utilised in various biological networks for drug repurposing.

Purpose: Efforts to produce radioprotective agents of high potential are appropriate strategies for overcoming possible IR toxicity in organisms. The present research aims to evaluate the signaling pathways and mechanisms through which arbutin exerts radioprotective effects on organisms. Methods: The databases of PubMed, Web of Sciences, Google Scholar, and Scopus were searched to find studies that reported radioprotective effects for arbutin. Besides, the data were searched within the time period from 2010 to 2020. Results: Five research articles met our criteria, which were included in the analysis based on their relevance to the topic. The present systematic review provides conclusions about various mechanisms and pathways through which arbutin induces radioprotection. Conclusions: Based on the relevant studies, various mechanisms can be proposed for inducing radioprotective effects by arbutin, including inhibition of oxidative stress, apoptosis, and inflammation.

Objective: This study aimed to compare the incidence of dementia and all-cause mortality up to 20 years post-treatment in an index non-demented cohort between antipsychotic (AP) medication treatment and non-AP treatment groups. Methods: All patients in Kaiser Permanente Northern California with a major psychiatric diagnosis between 01/01/1996 and 12/31/2000, age ≥ 50 years, and without dementia diagnosis were included. The study cohort was divided into a “user group”, patients treated with AP for ≥ 365 days (n = 1,829), and a “non-user group”, propensity score-matched on age, sex, and race (n = 9,145). The association between AP exposure and dementia or mortality during the follow-up period (01/01/2001–12/31/2015) was evaluated using Cox proportional hazard models adjusted for psychiatric diagnosis, comorbidities, and other medications. Results: The user group had a hazard ratio (HR) of 2.2 (CI 1.8–2.7) for dementia and 1.3 (CI 1.2- 1.5) for death. The onset of dementia in the user group was significantly higher in patients aged ≤ 65 years (p < 0.001). The user group was sub-grouped into atypical, typical, and both; HR for dementia was 1.7 (CI 1.2-2.4), 2.5 (CI 1.9-3.1), and 1.8 (CI 1.4–2.4), respectively. Dementia and mortality were significantly higher in patients concurrently treated with benzodiazepine (HR 1.3; CI 1.2-1.5 and HR 1.4; CI 1.3–1.5) or tricyclic antidepressants (HR 1.2; CI 1.1–1.4 and HR 1.1; CI 1.0-1.2), respectively. Conclusion: Our preliminary results reveal an association between AP treatment and increased rates of both dementia and mortality. Future research is needed to substantiate our current findings.

Background: Prunella vulgaris (PV) is a low-growing perennial herb, which can be found in different parts of the world as Asia, Europe and North America. It is traditionally used for medicinal treatment in various cultures in India, China, Japan, Korea, Russia, and Eastern Europe for treating different ailments, such as fever, and healing wounds. In our previous article, we showed the anti-tumorous effect of the volatile organic compounds (VOCs) of PV and characterized the steam distillation process in the extraction of VOCs from PV. This has never been done before as we are aware of. To use the VOCs as drugs, there is a question of how much of the VOCs are lost before the prepared drugs reach the patients. Thus, the first aim of the present article is to try to explore the time depletion effect on the VOCs in the PV extracts. Then, the second aim is to extend the work in the previous paper and further understand the dynamics of the distillation process of PV by changing the steam flow rate in the extraction process. Methods: To achieve the first aim to explore the aging effect of how much VOCs are depleted after they are extracted, the VOCs were first extracted by the same method as before, i.e., using steam distillation. Then, tubes of the aqueous solution containing the VOCs were then stored in a 5°C refrigerator. They were then taken out for GC-MS analysis according to a preplanned schedule up to 8 weeks after the VOCs were extracted. The chemical composition of the distillate could then be evaluated. This revealed the changes in the abundance of VOCs with aging. At the same time, the cell viability of SCC154 oral squamous cells treated by these herbal solutions, which were at different aging stages, was evaluated using a tetrazolium-based colorimetric reagent, Cell Counting Kit-8. To achieve the second aim of exploring the dynamics of the steam distillation process, the steam flow rate was adjusted by changing the temperature setting of the hot plate. GC-MS was again used to quantify the chemical constituents of the distillates. Results: By using GC-MS to measure the abundance of volatile compounds at different time points after the distillation process, it was found that the volatile compounds persist for a very long time, or over 8 weeks, which was the longest period of our experiment. The aging of the distillates also did not depreciate much the cell cytotoxicity of the PV distillate on the cancer cells. With respect to the dynamics of the steam distillation process, it was found that, at a low steam flow rate, volatile compounds of lower molecular weight are more efficient to be extracted, while at a high steam flow rate, volatile compounds of higher molecular weight are more efficiently extracted. Conclusion: Our findings demonstrate that the VOC compounds extracted and present in aqueous form do not deplete much for at least 2 months after the extraction process, neither they exhibit cell cytotoxicity. The experiments on the dynamics of the steam distillation process demonstrate that the mass of herb present in the flow path of the steam has significant effects on the relative amounts of VOCs extracted.